US2020115324A1PendingUtilityA1
Methods and compositions for substance use disorder vaccine formulations and uses thereof
Est. expiryJun 11, 2037(~10.9 yrs left)· nominal 20-yr term from priority
A61P 37/04A61K 39/385A61K 2039/55505A61P 25/30A61K 39/0013A61K 2039/55561A61K 2039/6012A61K 2039/6037C07C 233/54A61K 2039/627A61K 2039/55555
42
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention relates to vaccine compositions for treatment of substance use disorders, methods for the manufacture thereof, and methods for the use thereof to treat an animal. These compositions comprise a hapten conjugated via a linker to a protein scaffold and mixed with a particulate carrier and at least one immunostimulatory adjuvant molecule.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A compound or salt thereof, said compound having a general formula:
wherein
R1 is optionally substituted C 1-6 alkyl, wherein substitution(s), when present, may be independently selected from the group consisting of —NO 2 , —NH 2 , —OH, ═O, —COOR′ where R′ is H or lower alkyl, —CH 2 OH, and —CONH 2 ,
R2 is peptide of m amino acid residues, an alkylene oxide of m alkylene oxide monomers, or (CH 2 ) m , where m=2 to 6; and
R3 is a linkage chemistry which provides a terminal functional moiety selected from the group consisting of protected or unprotected sulfhydryl moieties, protected or unprotected amine moieties, protected or unprotected hydroxyl moieties, primary amine-reactive moieties, sulfhydryl-reactive moieties, photoreactive moieties, carboxyl-reactive moieties, arginine-reactive moieties, and carbonyl-reactive moieties.
2 . A compound or salt thereof according to claim 1 , wherein R1 is —(CH 2 ) n —, wherein n is 1 to 6.
3 . A compound or salt thereof according to claim 1 or 2 , wherein R2 is —(O—CH 2 —CH 2 ) p —, wherein p is 1 to 6.
4 . A compound or salt thereof according to claim 1 or 2 , wherein R2 is -Gly-Gly-, -Gly-Ala-, -Ala-Gly-, -Pro-Gly-, -Gly-Pro-, -Ala-Ala-, -Ala-Pro-, or -Pro-Ala-.
5 . A compound or salt thereof according to one of claims 1 - 4 , wherein R3 is a functional moiety selected from the group consisting of protected or unprotected sulfhydryl moieties, protected or unprotected amine moieties, protected or unprotected hydroxyl moieties, primary amine-reactive moieties, sulfhydryl-reactive moieties, photoreactive moieties, carboxyl-reactive moieties, arginine-reactive moieties, and carbonyl-reactive moieties.
6 . A compound or salt thereof according to one of claims 1 - 4 , wherein R3 is selected from the group consisting of a maleimide, an alkyl halide, an aryl halide, an alpha-haloacyl, an activated aryl, a pyridyl disulfide, a carbonyl, a carboxyl, a thiol, a thioester, disulfide, a N-hydroxy-succinimide, or a cyclic thiolactone.
7 . A compound or salt thereof according to claim 6 , wherein the compound has the structure
where R is a maleimide, an alkyl halide, an aryl halide, an alpha-haloacyl, an activated aryl, a pyridyl disulfide, a carbonyl, a carboxyl, a thiol, a thioester, disulfide, a N-hydroxy-succinimide, or a cyclic thiolactone.
8 . A compound according to claim 7 , wherein the compound is
9 . A conjugate comprising one or more compounds according to one of claims 1 - 8 covalently bound through the functional moiety on the compound(s) to a corresponding coupling site on a protein, polypeptide, detectable label, nucleic acid, or solid phase.
10 . A conjugate according to claim 9 , wherein the functional moiety is a sulfhydryl-reactive moiety.
11 . A conjugate according to claim 10 , wherein said sulfhydryl-reactive moiety is a maleimide.
12 . A conjugate according to claim 10 , wherein said sulfhydryl-reactive moiety is an alkyl halide, an aryl halide, an acryl, or an α-haloacyl, wherein the sulfhydryl-reactive moiety reacts with sulfhydryls to form thiol ether bonds.
13 . A conjugate according to claim 12 , wherein the functional moiety is a carbonyl-reactive moiety.
14 . A conjugate according to one of claims 9 - 13 , wherein said detectable label is selected from the group consisting of a hapten carrier protein comprising a T-helper epitope, an enzyme, a fluorophore, biotin, avidin, streptavidin, digoxigenin, maltose, oligohistidine, 2,4-dintrobenzene, phenylarsenate, a metal, a fluorescent or colored microsphere, a fluorescent particle, and a colored latex particle.
15 . A conjugate according to according to claim 14 , wherein said hapten carrier protein comprising a T-helper epitope is selected from the group consisting of keyhole limpet hemocyanin, bovine serum albumin, thyroglobulin, thioredoxin, ovalbumin, lysozyme, diphtheria antigen DT, diphtheria antigen CRM197 and tetanus toxoid.
16 . A method of preparing a conjugate, comprising:
contacting one or more compounds of one of claims 1 - 8 with a protein, polypeptide, detectable label, nucleic acid, or solid phase under conditions to provide covalent coupling of said compound(s) to said protein, polypeptide, detectable label, nucleic acid, or solid phase through a reactive moiety on the compound(s).
17 . A method according to claim 16 , wherein said compound(s) comprise a protected reactive moiety, and said method further comprises deprotecting said reactive moiety following, or together with, said contacting step.
18 . A method according to claim 16 or 17 , wherein said method further comprises introducing said one or more coupling sites corresponding to the reactive moiety into said protein, polypeptide, detectable label, nucleic acid, or solid phase prior to said contacting step.
19 . A method according to claim 18 , wherein said reactive moiety is a sulfhydryl-reactive moiety, and said introducing step comprises coupling of said protein, polypeptide, detectable label, nucleic acid, or solid phase to one or more bivalent crosslinkers comprising said one or more sulfhydryl-reactive moieties.
20 . A method of stimulating an immune response to methamphetamine, comprising:
immunizing an animal with a conjugate of one of claims 9 - 15 .
21 . A method according to claim 20 , wherein the animal is a human.
22 . A vaccine composition consisting of a hapten conjugated to a carrier; a particulate carrier vehicle; and one or more immunostimulatory adjuvant molecules.
23 . The vaccine composition of claim 22 , wherein the carrier is tetanus toxoid, diphtheria toxin CRM or thioredoxin.
24 . The vaccine composition according to one of claims 22 - 24 , wherein the particulate carrier vehicle is aluminum hydroxide or aluminum phosphate.
25 . A vaccine composition according to one of claims 22 - 24 , wherein the particulate carrier vehicle is a liposome.
26 . A vaccine composition according to claim 25 , wherein the liposome comprises phosphatidylcholine, a sterol, phosphatidylglycerol or phosphatidylethanolamine.
27 . A vaccine composition according to one of claims 22 - 24 , wherein the particulate carrier vehicle is an emulsion.
28 . A vaccine composition according to one of claims 22 - 27 , wherein the immunostimulatory adjuvant molecules comprise a Toll-like Receptor (TLR) agonist.
29 . A vaccine composition according to one of claims 22 - 28 , wherein the immunostimulatory adjuvant molecules comprise a STING agonist.
30 . A vaccine composition according to one of claims 22 - 29 , wherein the immunostimulatory adjuvant molecules comprise a C-type lectin receptor (CLR) agonist.
31 . A vaccine composition according to claim one of claims 22 - 30 , wherein the immunostimulatory adjuvant molecules comprise a NOD-like receptor (NLR) agonist.
32 . A vaccine composition according to one of claims 22 - 31 , wherein the immunostimulatory adjuvant molecules comprise a TLR2 agonist.
33 . A vaccine composition according to one of claims 22 - 32 , wherein the immunostimulatory adjuvant molecules comprise a TLR3 agonist.
34 . A vaccine composition according to one of claims 22 - 33 , wherein the immunostimulatory adjuvant molecules comprise a TLR4 agonist.
35 . A vaccine composition according to one of claims 22 - 34 , wherein the immunostimulatory adjuvant molecules comprise a TLR5 agonist.
36 . A vaccine composition according to one of claims 22 - 35 , wherein the immunostimulatory adjuvant molecules comprise a TLR7/8 agonist.
37 . A vaccine composition according to one of claims 22 - 36 , wherein the immunostimulatory adjuvant molecules comprise a TLR9 agonist.
38 . A vaccine composition according to one of claims 22 - 37 , wherein the immunostimulatory adjuvant molecules comprise a cyclic dinucleotide.
39 . A vaccine composition according to one of claims 22 - 38 , wherein the immunostimulatory adjuvant molecules comprise a muramyl di- or tri-peptide.
40 . A vaccine composition according to one of claims 22 - 39 , wherein the immunostimulatory adjuvant molecules comprise trehalose dibehenate.
41 . A vaccine composition according to according to one of claims 22 - 40 , wherein the hapten is a methamphetamine hapten.
42 . A vaccine composition according to according to one of claims 22 - 40 , wherein the hapten is an opioid hapten.
43 . A vaccine composition according to according to one of claims 22 - 40 , wherein the hapten is a nicotine hapten.
44 . A vaccine composition according to according to one of claims 22 - 40 , wherein the hapten is a cocaine hapten.
45 . A vaccine composition according to according to one of claims 22 - 44 , wherein the hapten is conjugated to the carrier via a linker.
46 . A vaccine composition according to claim 45 , wherein the linker comprises a peptide.
47 . A vaccine composition according to claim 45 or 46 , wherein the linker comprises an alkyl chain.
48 . A vaccine composition according to one of claims 45 - 47 , wherein the linker is polyethylene glycol.
49 . A vaccine composition according to one of claims 22 - 48 , wherein the hapten conjugated to a carrier is a conjugate according to one of claims 7 - 13 .
50 . A method of stimulating an immune response to methamphetamine, comprising:
immunizing an animal with a vaccine composition of one of claims 22 - 49 .
51 . A method according to claim 50 , wherein the animal is a human.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.